Obsidian in the forest: geochemistry of archaeological artifacts from SW Río Negro and NW Chubut (Patagonia, Argentina)

Presentamos nuevos datos acerca de la caracterización geoquímica de artefactos de obsidiana de sitios arqueológicos ubicados en el bosque mixto de Nothofagus y Austrocedrus del noroeste de la Patagonia, Argentina. Estos datos se suman a la información disponible para esta área, permitiéndonos discutir la distribución espacial y la circulación de obsidiana en el interior del bosque y entre este ambiente y la estepa, al este, y la costa del Pacífico, al oeste. Analizamos por ICP-MS la composición geoquímica de 32 artefactos arqueológicos de obsidiana de siete sitios ubicados en las localidades de El Manso, El Hoyo y Cholila. Estos datos indican la existencia de un eje de circulación norte-sur de obsidiana en el interior del bosque y otro eje de circulación este-oeste entre la estepa y el bosque a distancias considerables. No se ha encontrado obsidiana procedente de fuentes ubicadas en Chile. Los cazadores-recolectores comenzaron a habitar el bosque andino patagónico en el Holoceno Temprano. Sin embargo, hasta la realización de nuestro análisis no había registro del uso de la obsidiana dentro del ambiente de bosque hasta el Holoceno Tardío, cuando ocurrió la ocupación humana más intensa de estos espacios. Estos nuevos datos extienden la discusión temporal del uso de la obsidiana en el bosque al Holoceno Temprano.We present new data about the trace-element geochemistry of obsidian artifacts from archaeological sites located in the mixed Nothofagus and Austrocedrus forest of northwest Patagonia, Argentina. These data enlarge the available information in this field and allow us to discuss both the spatial distribution and the circulation of obsidian inside the forest and between this environment and both the steppes to the east and the Pacific coast to the west. We analyzed by ICP-MS the trace-element composition of 32 archaeological obsidian artifacts from seven sites located in the localities of El Manso, El Hoyo and Cholila. These data indicate north-south circulation of obsidian within the interior of the forest, and also east-west circulation over considerable distances between the steppes and the forest. No obsidian from sources in Chile has been found. Even though hunter-gatherers began to inhabit the Andean Patagonian forest in the Early Holocene, previous studies have not recorded the use of obsidian inside the forest environment until Late Holocene when the most intense human occupation of these spaces occurred. The new data presented here extends the temporal discussion of the use of obsidian in the forest back into the Early Holocene.Fil: Bellelli, Cristina Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; ArgentinaFil: Carballido Calatayud, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; ArgentinaFil: Stern, Charles. State University of Colorado at Boulder; Estados Unido

Genetic Variation in the Base Excision Repair Pathway, Environmental Risk Factors, and Colorectal Adenoma Risk

Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER). We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation

Nuclear microenvironments modulate transcription from low-affinity enhancers

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation

Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk

Migration from Mexico to the United States : a high-speedcancer transition

Q1Q1477-488Differences and similarities in cancer patterns between the country of Mexico and the United States' Mexican population, 11% of the entire US population, have not been studied. Mortality data from 2008 to 2012 in Mexico and California were analyzed and compared for causes of cancer death among adult and pediatric populations, using standard techniques and negative binomial regression. A total of 380,227 cancer deaths from Mexico and California were included. Mexican Americans had 49% and 13% higher mortality than their counterparts in Mexico among males and females, respectively. For Mexican Immigrants in the US, overall cancer mortality was similar to Mexico, their country of birth, but all‐cancers‐combined rates mask wide variation by specific cancer site. The most extreme results were recorded when comparing Mexican Americans to Mexicans in Mexico: with mortality rate ratios ranging from 2.72 (95% CI: 2.44–3.03) for colorectal cancer in males to 0.28 (95% CI: 0.24–0.33) for cervical cancer in females. These findings further reinforce the preeminent role that the environment, in its multiple aspects, has on cancer. Overall, mortality from obesity and tobacco‐related cancers was higher among Mexican origin populations in the US compared to Mexico, suggesting a higher risk for these cancers, while mortality from prostate, stomach, and especially cervical and pediatric cancers was markedly higher in Mexico. Among children, brain cancer and neuroblastoma patterns suggest an environmental role in the etiology of these malignancies as well. Partnered research between the US and Mexico for cancer studies is warranted

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Family history and risk of bladder cancer:an analysis accounting for first- and second-degree relatives

Although evidence suggests that a positive family history of bladder cancer in first-degree relatives is an important risk factor for bladder cancer occurrence, results remain unclear. The influence of family history of non-bladder cancers and more distant relatives on bladder cancer risk is inconsistent. This research therefore, aims to increase the understanding of the association between family history and bladder cancer risk based on worldwide case-control studies. In total 4,327 cases and 8,948 non-cases were included. Pooled odds ratios (ORs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel logistic regression models, adjusted by age, sex, ethnicity, smoking status, and smoking pack-years. The results show bladder cancer risk increased by having a first- or second-degree relative affected with bladder cancer (OR 2.72, 95%CI 1.55-4.77 and OR 1.71, 95%CI 1.22-2.40, respectively), and non-urologic cancers (OR 1.61, 95%CI 1.19-2.18). Moreover, bladder cancer risk increased by number of cancers affected first-degree relatives (for 1 and >1 first-degree relatives: OR 1.42, 95% CI 1.02-2.04; OR 2.67, 95% CI 1.84-3.86, respectively). Our findings highlight an increased bladder cancer risk for a positive bladder cancer family history in first- and second-degree relatives, and indicate a possible greater effect for an increment of numbers of affected relatives

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad Line Region in Mrk 50

We present dynamical modeling of the broad line region (BLR) in the Seyfert 1 galaxy Mrk 50 using reverberation mapping data taken as part of the Lick AGN Monitoring Project (LAMP) 2011. We model the reverberation mapping data directly, constraining the geometry and kinematics of the BLR, as well as deriving a black hole mass estimate that does not depend on a normalizing factor or virial coefficient. We find that the geometry of the BLR in Mrk 50 is a nearly face-on thick disk, with a mean radius of 9.6(+1.2,-0.9) light days, a width of the BLR of 6.9(+1.2,-1.1) light days, and a disk opening angle of 25\pm10 degrees above the plane. We also constrain the inclination angle to be 9(+7,-5) degrees, close to face-on. Finally, the black hole mass of Mrk 50 is inferred to be log10(M(BH)/Msun) = 7.57(+0.44,-0.27). By comparison to the virial black hole mass estimate from traditional reverberation mapping analysis, we find the normalizing constant (virial coefficient) to be log10(f) = 0.78(+0.44,-0.27), consistent with the commonly adopted mean value of 0.74 based on aligning the M(BH)-{\sigma}* relation for AGN and quiescent galaxies. While our dynamical model includes the possibility of a net inflow or outflow in the BLR, we cannot distinguish between these two scenarios.Comment: Accepted for publication in ApJ. 8 pages, 6 figure

Nuclear microenvironments modulate transcription from low-affinity enhancers

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation